Author/Editor		Vrbova, Gerta; Hausmanowa-Petrusewicz, Irena
Title		Biology of some neuromuscular disorders
Translated title		Biologija nekaterih živčnomišičnih bolezni
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 73, št. Suppl 2
Publication year		2004
Volume		str. II-3-10
Language		eng
Abstract		In order to understand and possibly interfere/ treat neuromuscular disorders it is important to analyze the biological events that may be causing the disability. We illustrate such attempts on two examples of genetically determined neuromuscular diseases: 1) Duchenne muscular dystrophy (DMD), and 2) Spinal muscular atrophy (SMA). DMD is an x-linked hereditary muscle disease that leads to progressive muscle weakness. The altered gene in DMD affects dystrophin, a muscle membrane associated proteine. Attempts were made to replace the deficient or missing gene / protein into muscles of Duchenne children. Two main strategies were explored: 1) Myoblast and stem cell transfer and 2) Gene delivery. The possible use of methods other than the introduction of the missing gene for dystrophin into muscle fibres are based on the knowledge about the adaptive potential of muscle to different functional demands and the ability of the muscle to express a new set of genes in response to such stimuli. Stretch or overload is now known to lead to changes of gene expression in normal muscle, and the success of muscle stretch in the management of Duchenne boys is most likely to be due to such adaptive changes. Electrical stimulation of muscles is also a powerful stimulus for inducing the expression of new genes and this method too has produced beneficial effects on the progress of the disease in mice and men. SMA is a heterogeneous group of hereditary neuromuscular disorders where the loss of lower motoneurones leads to progressive weakness and muscle atrophy. The disease subdivides into 3 forms according to the severity of the symptoms and age of onset. All three forms of SMA have been mapped to chromosome Sq11.2-13.2. Clinical features of all these forms of SMA include hypotonia shortly after birth, symmetrical muscle weakness and atrophy, finger tremor, areflexia or hyporeflexia and later contractures. (Abstract truncated at 2000 characters).
Summary		Živčnomišične bolezni bomo bolje razumeli in morebiti zdravili le na podlagi analize bioloških procesov, ki povzročajo prizadetost. V prispevku predstavljamo poskuse takšne analize na dveh primerih iz skupine dednih živčnomišičnih bolezni: 1) Duchennove mišične distrofije (DMD) in spinalne mišične atrofije (SMA). DMD je na x-kromosom vezana dedna bolezen mišic, ki povzroča napredujočo mišično šibkost. Patološko spremenjeni gen, ki povzroča DMD, določa na mišično celično membrano vezani protein distrofin. Poskusi nadomestiti patološko spremenjeni gen/protein v mišicah so bili že napravljeni z uporabo prenosa mioblastov in zarodnih celic ter neposrednega vnosa dednine/gena v mišice dečkov z DMD. Drugi smiselni terapevtski pristopi bi lahko temeljili na razumevanju adaptacijskih zmožnosti skeletne mišice na različne funkcijske zahteve in dokazane zmožnosti ekspresije novih nizov genov v mišičnih celicah v odgovor na takšne zahteve. Nateg ali prekomerna obremenitev normalnih mišičnih celic vodita v spremenjeno ekspresijo genov v mišicah, verjetno pa lahko terapevtske uspehe razteznih vaj oziroma uporabe ortoz v te namene pri dečkih z DMD pripišemo istemu mehanizmu mišične adaptacije. Tudi električna stimulacija je močan stimulus indukcije ekspresije novih genov. Njeni ugodni učinki na napredovanje mišične distrofije so že dokazani tako na živalskem modelu (miš) kot na človeku. Spinalna mišična atrofija je klinično heterogena skupina dednih živčnomišičnih bolezni, za katero je značilna izguba spodnjih motoričnih nevronov z napredujočo mišično šibkostjo in mišičnimi atrofijami. SMA se deli v tri oblike glede na stopnjo izraženosti bolezni in na starost ob pojavu bolezni. Vse tri oblike SMA so vezane na peti kromosom (Sq11.2-13.2), to je na regijo, ki določa gen SMN ("survival motoneuron gene"). (Izvleček skrajšan pri 2000 znakih).
Descriptors		NEUROMUSCULAR DISEASES MUSCULAR DYSTROPHY MUSCULAR ATROPHY, SPINAL DYSTROPHIN GENE THERAPY GENE EXPRESSION MUSCLE FIBERS MOTOR NEURONS ELECTRIC STIMULATION